Genome instability from nuclear catastrophe and DNA damage.

The nuclear envelope compartmentalizes the eukaryotic genome, provides mechanical resistance, and regulates access to the chromatin. However, recent studies have identified several conditions where the nuclear membrane ruptures during interphase, breaking down this compartmentalization leading to DNA damage, chromothripsis, and kataegis. This review discusses three major circumstances that promote nuclear membrane rupture, nuclear deformation, chromatin bridges, and micronucleation, and how each of these nuclear catastrophes results in DNA damage. In addition, we highlight recent studies that demonstrate a single chromosome missegregation can initiate a cascade of events that lead to accumulating damage and even multiple rounds of chromothripsis.